I. Field of the Invention
Embodiments of this invention are directed generally to biology and medicine. In certain aspects, embodiments are directed to compositions and methods related to Tau oligomers and Tau oligomer specific antibodies.
II. Background
Pathological aggregation of the microtubule-associated protein Tau and accumulation of neurofibrillary tangles (NFT) or other inclusions containing Tau are defining histopathological features of Alzheimer's disease (AD) and many neurodegenerative diseases collectively known as tauopathies, including Pick's disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and frontotemporal lobar degeneration (FTLD). The correlation between neurofibrillary tangles (NFT) and disease progression has been studied extensively with conflicting results, and the mechanisms linking the pathological aggregation of Tau with synaptic dysfunction and neurodegeneration are poorly understood.
In the case of Alzheimer's disease, current pharmaceutical therapies are focused on symptomatic treatment of the loss of cholinergic transmission which results from neurodegeneration (Mayeux et al., 1999). However, although the available treatments delay progression of the disease for up to six to twelve months, they do not prevent it. The discovery of drugs that could prevent the aggregation of Tau which leads to neurodegeneration would provide a more effective strategy for prophylaxis or for inhibiting the progression of the disease, which would not require an immediate knowledge of the diverse upstream events that initiate the aggregation.
Furthermore, the clinical diagnosis of Alzheimer's disease (AD) is difficult to make, especially in early stages of the disease. Today, the diagnosis is based on a typical medical history combined with the exclusion of other causes of dementia. Certain clinical centers can have a diagnostic accuracy of 85-90% compared with the neuropathological diagnosis. In the early stages of the disease the clinical picture is vague and definite diagnostic markers have not yet been identified (McKhann 1984). The development of biochemical diagnostic markers is important for a number of reasons: to support the clinical diagnosis, to allow clinicians to give adequate information to patients and their relatives, to initiate pharmacological treatment and care-giving, and in various aspects of clinical research.
Thus, in view of the prior art techniques for preventing and treating tauopathies, there is a need for a technique that enables earlier detection of markers of Alzheimer's disease and other tauopathies. If said markers could be prevented without causing negative side-effects, this would be a means to prevent and treat Alzheimer's disease at an early stage. Any treatment of Alzheimer's disease that would reduce the amount of Tau insoluble aggregates in the brain of AD patients, would be of significant therapeutic value.